Human blood monocytes interact with type I collagen through alpha(x)ss(2) integrin (CD11c-CD18, gp150-95)

Human blood monocytes are attracted into connective tissues during early st eps of inflammation and wound healing, and locally interact with resident c ells and extracellular matrix proteins. We studied the effects of type I co llagen on monocyte adhesion and superoxide anion production, using human mo nocytes elutriated from peripheral blood and type I collagen obtained from rat tail tendon, Both acid-soluble and pepsin-digested type I collagens pro moted the adhesion of monocytes, whereas only acid-soluble collagen with in tact telopeptides induced the production of superoxide, Adhesion and activa tion of monocytes on acid-soluble type I collagen depended on the presence of divalent cations, mAbs directed against integrin subunits CD11c and CD18 specifically inhibited adhesion and activation of monocytes on type I coll agen. Protein membrane extracts obtained from monocytes were submitted to a ffinity chromatography on collagen I-Sepharose 4B, and analyzed by Western blotting using specific anti-integrin subunit Abs, In the case of both acid -soluble and pepsin-digested collagens, two bands were revealed with mAbs a gainst CD11c and CD18 integrin subunits, Our results demonstrate that monoc ytes interact with type I collagen through CD11c-CD18 (alpha(x)beta(2)) int egrins, which promote their adhesion and activation, For monocyte activatio n, specific domains of the type I collagen telopeptides are necessary, Inte ractions between monocytes and collagen are most likely involved in the cas cade of events that characterize the initial phases of inflammation.